Six sero-negative, culture-negative young adult chimpanzees were inoculated intratracheally with an early passage of virulent Mycoplasma pneumoniae strain PI-1428. Each chimpanzee became colonized with peak respiratory mycoplasma titers of 10 to the 6 to 10 to the 8 ccu/ml. Oropharyngeal and tracheal tissues remained colonized for up to 70 days and lungs remained colonized for 26 days. Animals developed positive X-ray findings by day 12 to 16 which corresponded with peak lung colonization. Positive cold agglutinin serum titers were first observed at day 12 to 15 post- inoculation, and persisted for up to 48 days with peak titers ranging from 1:160 to 1:640. Serum antibody titers, determined by the metabolic inhibition test, developed within two weeks and persisted throughout the three month study period. Animals showed overt signs of clinical disease within two weeks post-inoculation which corresponded with the onset of positive X-ray findings, the development of cold agglutinins and peak colonization of lungs. All animals developed a persistent cough and some developed rhinitis, inflamed oropharyngeal tissues, diarrhea, and loss of appetite. Low grade fever was seen in three of the infected animals. Lung lavage fluids and sera contained M. pneumoniae-specific IgA and IgG immunoglobulins with up to five-fold higher values in the lung washings than in the serum as determined by a radio-immunoassay. Two control chimpanzees maintained in individual cages and in rooms separated and distant from the infected animals became infected on days 19 and 48, respectively. Although we were unable to determine the means of transmission, this represents the first report of M. pneumoniae disease transmission in an animal model. Unlike all other animals tested, chimpanzees become overtly ill and develop positive X-ray findings and cold agglutinin titers. Thus the M. pneumoniae pneumonias induced in chimpanzees are remarkably similar to naturally occurring primary atypical pneumonia in humans and the infection in the chimpanzee animal model best reflects and parallels pneumonia in humans.